The overall objective of this research proposal is the development of preclinical information for delivery of more effective oncolytic drug therapy to children. The major emphasis during the next year will be on the more therapeutically promising observations of the current year. As presently projected, these are clinical and preclinical studies of the treatment with "high-dose" MTX and leucovorin rescue, preclinical studies on the biochemical basis for the oncolytic interaction between Ara-C and MTX, and preclinical studies on the potentiation of ARA-C by VM26. As time permits, studies of the biochemical response to adriamycin plus cyclophosphamide as well as the effect on life span by various drugs and two-drug combinations in sequence will be studied with mice bearing transplantable tumors. BIBLIOGRAPHIC REFERENCES: Avery, T.L., and Roberts, D.: Adriamycin and cyclophosphamide in combination chemotherapy of L1210 leukemia. Cancer Res. 36: 1976. Roberts, D., and Avery, T.L.: On the biochemical basis for synergism between methotrexate (MTX) and cytarabine (Ara-C). Proc. Am. Assoc. Cancer Res. 17: 97, 1976, abstract.